Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.     

Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron

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Efficacy and safety of cold snare polypectomy for sessile serrated polyps ≥ 10 mm: A systematic review and meta-analysis

BackgroundCold snare polypectomy (CSP) is a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. However, the efficacy and safety of this technique remain undetermined.AimsWe aimed to comprehensively evaluate the efficacy and safety of CSP for SSPs ≥ 10 mm.MethodsPubMed, EMBASE, Web of Science and Cochrane Library were searched up to January 2021.ResultsA total of 10 studies consisting of 1727 SSPs (range, 10–40 mm) from 1021 patients were included. The overall rates of technical success, adverse events (AEs) and residual SSPs were 100%, 0.7% and 2.9%, respectively. Subgroup analysis showed that the rates of technical success and AEs were comparable between CSP and cold endoscopic mucosal resection (EMR) (99.9% vs. 100% and 1.3% vs. 0.5%, respectively), between the proximal and distal colon (100% vs. 99.9% and 0.3% vs. 0, respectively), and between polyps of 10–19 mm and ≥20 mm (99.8% vs. 100% and 0.9% vs. 0, respectively). However, subgroup analysis showed that the rate of residual SSPs was slightly lower in CSP compared with cold EMR (1.3% vs. 3.9%), as well as in polyps of 10–19 mm compared with those ≥20 mm (3.1% vs. 4.7%).ConclusionCSP was an effective and safe technique for removing SSPs ≥ 10 mm.     

Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy. The reactivation of oncogenic viruses has also been alluded to in the context and following COVID-19. Paradoxically, certain tumors responded better following the profound infection-induced immune modulation. Unveiling the mechanisms of the virus-tumor cell interactions will lead to a better understanding of the pathophysiology of both cancer progression and virus propagation. It would be challenging to monitor, through the different cancer registries, retrospectively, the response of patients who have been previously exposed to the virus in contrast to those who have not contracted the infection.     

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system

IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.